Special Issue Information

Dear Colleagues,

The age-related decrease in muscle health is a main limiting factor for functional independence and longevity. Nutrient provision and physical activity are two key regulators of muscle function. Specifically, amino acids and dietary proteins influence muscle protein kinetics in response to endurance and weight-bearing exercise. This special issue will highlight emerging research on interactions between amino acids, dietary proteins, and exercise training that have potential to impact muscle health and biology.

Abstract: Ingestion of protein is crucial for maintenance of a variety of body functions and within the scope of this review we will specifically focus on the regulation of skeletal muscle mass. A quantitative limitation exists as to how much muscle protein the body can synthesize in response to protein intake. Ingestion of excess protein exerts an unwanted load to the body and therefore, it is important to find the least amount of protein that provides the maximal hypertrophic stimulus. Hence, research has focused on revealing the relationship between protein intake (dose) and its resulting stimulation of muscle protein synthesis (response). In addition to the protein amount, the protein digestibility and, hence, the availability of its constituent amino acids is decisive for the response. In this regard, recent studies have provided in-depth knowledge about the time-course of the muscle protein synthetic response dependent on the characteristics of the protein ingested. The effect of protein intake on muscle protein accretion can further be stimulated by prior exercise training. In the ageing population, physical training may counteract the development of “anabolic resistance” and restore the beneficial effect of protein feeding. Presently, our knowledge is based on measures obtained in standardized experimental settings or during long-term intervention periods. However, to improve coherence between these types of data and to further improve our knowledge of the effects of protein ingestion, other investigative approaches than those presently used are requested.

Abstract: Dexamethasone (DEXA) is a potent immunosupressant and anti-inflammatory agent whose main side effects are muscle atrophy and insulin resistance in skeletal muscles. In this context, leucine supplementation may represent a way to limit the DEXA side effects. In this study, we have investigated the effects of a low and a high dose of leucine supplementation (via a bolus) on glucose homeostasis, muscle mass and muscle strength in energy-restricted and DEXA-treated rats. Since the leucine response may also be linked to the administration of this amino acid, we performed a second set of experiments with leucine given in bolus (via gavage) versus leucine given via drinking water. Leucine supplementation was found to produce positive effects (e.g., reduced insulin levels) only when administrated in low dosage, both via the bolus or via drinking water. However, under DEXA treatment, leucine administration was found to significantly influence this response, since leucine supplementation via drinking water clearly induced a diabetic state, whereas the same effect was not observed when supplied viathe gavage.

Abstract: This study aimed to determine the effects of diets chronically supplemented with branched-chain amino acids (BCAA) on the fatigue mechanisms of trained rats. Thirty-six adult Wistar rats were trained for six weeks. The training protocol consisted of bouts of swimming exercise (one hour a day, five times a week, for six weeks). The animals received a control diet (C) (n = 12), a diet supplemented with 3.57% BCAA (S1) (n = 12), or a diet supplemented with 4.76% BCAA (S2) (n = 12). On the last day of the training protocol, half the animals in each group were sacrificed after one hour of swimming (1H), and the other half after a swimming exhaustion test (EX). Swimming time until exhaustion was increased by 37% in group S1 and reduced by 43% in group S2 compared to group C. Results indicate that the S1 diet had a beneficial effect on performance by sparing glycogen in the soleus muscle (p < 0.05) and by inducing a lower concentration of plasma ammonia, whereas the S2 diet had a negative effect on performance due to hyperammonemia (p < 0.05). The hypothalamic concentration of serotonin was not significantly different between the 1H and EX conditions. In conclusion, chronic BCAA supplementation led to increased performance in rats subjected to a swimming test to exhaustion. However, this is a dose-dependent effect, since chronic ingestion of elevated quantities of BCAA led to a reduction in performance.

Abstract: Previous research demonstrates that the anabolic response of muscle protein synthesis (MPS) to a meal is regulated at the level of translation initiation with signals derived from leucine (Leu) and insulin to activate mTORC1 signaling. Recent evidence suggests that the duration of the meal response is limited by energy status of the cell and inhibition of translation elongation factor 2 (eEF2). This study evaluates the potential to extend the anabolic meal response with post-meal supplements of Leu or carbohydrates. Adult (~256 g) male Sprague-Dawley rats were food deprived for 12 h, then either euthanized before a standard meal (time 0) or at 90 or 180 min post-meal. At 135 min post-meal, rats received one of five oral supplements: 270 mg leucine (Leu270), 80:40:40 mg leucine, isoleucine, and valine (Leu80), 2.63 g carbohydrates (CHO2.6), 1 g carbohydrates (CHO1.0), or water (Sham control). Following the standard meal, MPS increased at 90 min then declined to pre-meal baseline at 180 min. Rats administered Leu270, Leu80, CHO2.6, or CHO1.0 maintained elevated rates of MPS at 180 min, while Sham controls declined from peak values. Leu80 and CHO1.0 treatments maintained MPS, but with values intermediate between Sham controls and Leu270 and CHO2.6 supplements. Consistent with MPS findings, the supplements maintained elongation activity and cellular energy status by preventing increases in AMP/ATP and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase ACC and eEF2. The impact of the supplements on MPS and cellular energy status was in proportion to the energy content within the individual treatments (i.e., Leu270 > Leu80; CHO2.6 > CHO1.0), but the Leu supplements produced a disproportionate anabolic stimulation of MPS, eEF2 and energy status with significantly lower energy content. In summary, the incongruity between MPS and translation initiation at 180 min reflects a block in translation elongation due to reduced cellular energy, and the extent to which Leu or carbohydrate supplements are able to enhance energy status and prolong the period of muscle anabolism are dose and time-dependent.

Abstract: The loss of muscle mass and strength with aging (i.e., sarcopenia) has a negative effect on functional independence and overall quality of life. One main contributing factor to sarcopenia is the reduced ability to increase skeletal muscle protein synthesis in response to habitual feeding, possibly due to a reduction in postprandial insulin release and an increase in insulin resistance. Branched-chain amino acids (BCAA), primarily leucine, increases the activation of pathways involved in muscle protein synthesis through insulin-dependent and independent mechanisms, which may help counteract the “anabolic resistance” to feeding in older adults. Leucine exhibits strong insulinotropic characteristics, which may increase amino acid availability for muscle protein synthesis, reduce muscle protein breakdown, and enhance glucose disposal to help maintain blood glucose homeostasis.

Abstract: The aim of this study was to evaluate the effects of egg white protein compared to carbohydrate intake prior to exercise on fat free mass (FFM), one repetition maximum (1RM) muscle strength and blood biochemistry in female athletes. Thirty healthy female collegiate athletes were recruited for this study and matched by sport type, body fat percentage and 1RM leg curl muscle strength. Participants were randomly divided into two groups: protein group (15.0 g egg white protein; 75 kcal) and carbohydrate group (17.5 g maltodextrin, 78 kcal). Supplements were administered daily at the same time in a double-blind manner prior to training during an 8-week period. Measurements were performed before and after the 8-week regimen. The mean dietary energy intake did not change throughout the study period. FFM and 1RM assessments (i.e., leg curl, leg extension, squat, and bench press) increased in both groups. Furthermore, serum urea and serum citrulline levels after the 8-week regimen increased significantly only in the protein group. Our findings indicated that compared to the carbohydrate supplement, the protein supplement was associated with some changes in protein metabolites but not with changes in body composition or muscle strength.

Abstract: A series of complex intracellular networks influence the regulation of skeletal muscle protein turnover. In recent years, studies have examined how cellular regulators of muscle protein turnover modulate metabolic mechanisms contributing to the loss, gain, or conservation of skeletal muscle mass. Exercise and amino acids both stimulate anabolic signaling potentially through several intracellular pathways including the mammalian target of rapamycin complex 1 and the mitogen activated protein kinase cell signaling cascades. As novel molecular regulators of muscle integrity continue to be explored, a contemporary analysis of the literature is required to understand the metabolic mechanisms by which contractile forces and amino acids affect cellular process that contribute to long-term adaptations and preservation of muscle mass. This article reviews the literature related to how exercise and amino acid availability affect cellular regulators of skeletal muscle mass, especially highlighting recent investigations that have identified mechanisms by which contractile forces and amino acids modulate muscle health. Furthermore, this review will explore integrated exercise and nutrition strategies that promote the maintenance of muscle health by optimizing exercise, and amino acid-induced cell signaling in aging adults susceptible to muscle loss.